1. Date of download: 6/3/2016 Copyright © 2016 American Medical Association. All rights reserved. From: γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment Arch Gen Psychiatry. 2006;63(9):957-968. doi:10.1001/archpsyc.63.9.957 Range of ethanol concentrations with modulatory effects at selected ionotropic receptors. Each bar is black up to the concentration at which ethanol produces 50% of its maximum effect (EC 50 ) or the concentration at which ethanol produces a 50% inhibition of ligand binding to a receptor target (IC 50 ) (ie, the boundary of the black and gray sections of the bars). The ranges primarily reflect electrophysiologic data reviewed by Grant and Lovinger (where additional details related to the EC 50 or IC 50 values can be found). The figure has been modified to include studies reviewed in the text and to be consistent with a recent review. The clinical consequences of intoxication, also from Grant and Lovinger, vary across individuals depending on the initial level of alcohol sensitivity and extent of alcohol tolerance. 5-HT3 indicates serotonin type 3; GABA A, γ-aminobutyric acid type A; NMDA, N-methyl- D-aspartate. Figure Legend:

2. Date of download: 6/3/2016 Copyright © 2016 American Medical Association. All rights reserved. From: γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment Arch Gen Psychiatry. 2006;63(9):957-968. doi:10.1001/archpsyc.63.9.957 Relationship between the duration of sobriety and the volume of distribution of iodine I123-labeled iomazenil ( 123 I-iomazenil) in the medial frontal cortex (mFC) (open circles) and cerebellum (CB) (filled circles) in recovering alcohol-dependent nonsmoking (mFC: r = 0.72, P =.04; and CB: r = 0.93, P =.001) (A) and smoking (B) patients. The 123 I-iomazenil volume of distribution provides a measure related to the density of the benzodiazepine binding site of γ-aminobutyric acid type A receptors. Each dot represents data from an individual. Data are from Staley et al. Figure Legend:

3. Date of download: 6/3/2016 Copyright © 2016 American Medical Association. All rights reserved. From: γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment Arch Gen Psychiatry. 2006;63(9):957-968. doi:10.1001/archpsyc.63.9.957 The general trajectory of selected γ-aminobutyric acid type A (GABA A ) receptor subunits during alcohol dependence and the initiation of sobriety. The results of several studies considered in this review are summarized. The gross estimate of the percentage of GABA A receptors bearing a given subunit is based on the reported percentage of receptor subtypes in the brain from Whiting and on the quantitative time-dependent description of GABA A receptor subunit gene expression levels during ethanol withdrawal from Sanna et al. In the basal state, the synaptic GABA A receptors bearing the α 1-3, β 2-3, and γ 2 subunits dominate. With the development of alcohol dependence, synaptic and extrasynaptic receptor subunit composition changes, with α 4,6 subunits replacing α 1-3 subunits and γ 2 subunits replacing δ subunits. The GABA A receptors associated with alcohol dependence are less functional than the array associated with the basal state. In response, synaptic forms of GABA A receptors are recruited during acute withdrawal. The recent single-photon emission computed tomography data suggest that there is a transitional period during the late phase of acute withdrawal in which receptors associated with alcohol dependence are still present but the synaptic receptors are reemerging. This transitional period is associated with increased GABA A receptor density. As the transition to the basal array of GABA A receptor is completed (1 week to 1 month of sobriety), the GABA A receptor contribution to acute and protracted alcohol withdrawal is presumed to be completed. It is possible, however, that intracellular disturbances downstream of GABA A receptors may have a more protracted time course than that presented in this figure. Figure Legend: